Diisopropylethylamine → HCID 67606455, compound

HRID 1965196Notes

Reaction equation

HRID 1965196 reaction equation
[CH:1]([NH:4][C:5]([N:7]1[CH2:11][CH:10]([OH:12])[CH:9]2[NH:13][CH2:14][CH2:15][CH:8]12)=[O:6])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:73]([C:82]([O:84][CH2:85][C:86]1[CH:91]=[CH:90][CH:89]=[CH:88][CH:87]=1)=[O:83])[C@H:74]([C:79](O)=[O:80])[C:75]([CH3:78])([CH3:77])[CH3:76]>CN1C(=O)CCC1.O>[CH2:85]([O:84][C:82](=[O:83])[NH:73][CH:74]([C:79]([N:13]1[CH2:14][CH2:15][CH:8]2[N:7]([C:5](=[O:6])[NH:4][CH:1]([CH3:3])[CH3:2])[CH2:11][CH:10]([OH:12])[CH:9]12)=[O:80])[C:75]([CH3:76])([CH3:77])[CH3:78])[C:86]1[CH:91]=[CH:90][CH:89]=[CH:88][CH:87]=1

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67607035HCID 67607035, compoundHCID 131730509HCID 131730509, compound

Product 1

HCID 67606455HCID 67606455, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution containing crude 54 (˜3.8 g, 17.9 mmol) and DIPEA (4.1 mL, 23.3 mmol) in NMP (50 mL) was cooled to 0° C. In a separate flask, Cbz-Tle-OH dicyclohexylamine salt (8.8 g, 19.7 mmol), HATU (7.5 g, 19.7 mmol), and DIPEA (4.1 mL, 23.3 mmol) were dissolved in NMP (130 mL) at 0° C. A portion of the HATU/Cbz-Tle-OH solution (117 mL, ˜1.0 equiv) was added to the solution containing 54. After 30 min, the reaction mixture was diluted with water and extracted with 1:1 Et2O/EtOAc. The combined organic extracts were washed successively with 10% H3PO4, water, saturated aqueous NaHCO3, water, and brine, dried over anhydrous Na2SO4, filtered, and concentrated to afford 7.2 g of 55 as a beige-colored foam (88%, 4 steps) which was used without further purification. Mass spectrum, m/z [460.9] (M+H)+.

Workup

  1. additioncontaining 54
  2. extractionextracted with 1:1 Et2O/EtOAc
  3. washThe combined organic extracts were washed successively with 10% H3PO4, water, saturated aqueous NaHCO3, water, and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-5a8d407c6d584feeb39ce386609e17f3
Source dataset
uspto-grants-2013_04
Patent number
US08415486B2

Reaction notes

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